Genotypic tropism testing of proviral <scp>DNA</scp> to guide maraviroc initiation in aviraemic subjects: 48‐week analysis of results from the <scp>PROTEST</scp> study

Poveda, Eva; Hernández-Quero, José; Pérez-Elías, MJ; Ribas, Mª Angels; Martínez-Madrid, OJ; Flores, Juan; Navarro, Jordi; Gutiérrez, Félix; García-Deltoro, Miguel; Imaz, Arkaitz; Ocampo, Antonio; Artero, Arturo; Blanco, Francisco J.; Bernal, Enrique; Pasquau, Juan; Mínguez-Gallego, Carlos; Perez, Nieves Sanz; Aiestarán, Aintzane; García, Féderico; Paredes, Roger

doi:10.1111/hiv.12479

Cited by 1 publication

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References 17 publications

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“…However, use of TDF is associated with modest reductions in renal function and bone density [6][7][8] and may be contraindicated in some individuals. Maraviroc (MVC) is approved for the treatment of chronic HIV infection, but is only active against CCR5-tropic virus and its use requires prior characterization of the patientś viral tropism [9] . MVC has an excellent safety profile [10] .…”

Section: Introductionmentioning

confidence: 99%

The pharmacokinetics, pharmacodynamics, and mucosal responses to maraviroc-containing pre-exposure prophylaxis regimens in MSM

McGowan

Wilkin

Landovitz³

et al. 2019

Aids

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HPTN 069/ACTG A5305 was a study of 48-week oral PrEP regimens in MSM and transgender women A rectal substudy was included to evaluate drug concentrations in rectal compartment vs. blood, gut-associated lymphoid tissue (GALT) responses to four antiretroviral (ARV) PrEP regimens (maraviroc (MVC), MVC + emtricitabine (FTC), MVC + tenofovir disoproxil fumarate (TDF), and TDF + FTC), and to determine whether ARV exposure was associated with ex vivo suppression of HIV infection in colorectal explants. Methods: CCR5 genotype was characterized using PCR. At baseline and at weeks 24, 48, and 49, GALT phenotype was characterized by flow cytometry, rectal biopsies were challenged with HIV-1 BaL , and tissue and plasma pharmacokinetics were measured via mass spectrometry. Results: Exposure to MVC was not associated with increased expression of CD4+/CCR5+ HIV target T-cells. Significant ex vivo viral suppression compared to baseline was seen at Weeks 24 and 48, ranging from 1.4 to 1.8 log 10 for all study regimens except the MVC-alone arm which did not show statistically significant viral suppression at Week 48. Tissue concentrations of tenofovir (TFV), TFV-diphosphate (DP), and FTC were correlated with viral suppression. Conclusions: MVC-containing HIV PrEP regimens did not increase GALT CD4+ T-cell activation or the CD4+/CCR5+ phenotype. No virologic suppression was seen with MVC-alone at Week 48 compared to combination regimens, suggesting MVC monotherapy might be less effective than combination ARV PrEP regimens.

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Section: Introductionmentioning

confidence: 99%

The pharmacokinetics, pharmacodynamics, and mucosal responses to maraviroc-containing pre-exposure prophylaxis regimens in MSM

McGowan

Wilkin

Landovitz³

et al. 2019

Aids

View full text Add to dashboard Cite

show abstract

Genotypic tropism testing of proviral DNA to guide maraviroc initiation in aviraemic subjects: 48‐week analysis of results from the PROTEST study

Abstract: Initiation of MVC plus two NRTIs in aviraemic subjects based on genotypic tropism testing of proviral HIV-1 DNA is associated with low rates of virological failure for up to 1 year.

Cited by 1 publication

References 17 publications

The pharmacokinetics, pharmacodynamics, and mucosal responses to maraviroc-containing pre-exposure prophylaxis regimens in MSM

The pharmacokinetics, pharmacodynamics, and mucosal responses to maraviroc-containing pre-exposure prophylaxis regimens in MSM

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